台湾ALS患者的TARDBP变异:遗传谱,临床特征和创始人效应
Kang-Yang Jih1, Shih-Yu Fang2, Yu-Sheun Tsai3
1Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Neurology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan; Department of Physiology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan.
Journal of the neurological sciences
|May 15, 2025
概括
致病性TARDBP基因变异是台湾肌缩侧面硬化症 (ALS) 的重要原因,与早期发病和不完全透有关. 像M337V和S375G这样的常见变体表明台湾人口中存在创始人效应.
科学领域:
- 神经遗传学 神经遗传学
- 分子生物学分子生物学
- 临床神经学 临床神经学
背景情况:
- TARDBP基因编码TAR DNA结合蛋白43 (TDP-43),这是肌缩侧硬化症 (ALS) 病理学的关键蛋白.
- TARDBP中的致病变体破坏了TDP-43的正常功能,导致聚合并导致ALS.
- 研究TARDBP变体对于了解ALS遗传基础至关重要.
研究的目的:
- 调查台湾ALS队列中TARDBP变异的流行率和特征.
- 确定TARDBP变体与台湾ALS临床特征之间的关联.
- 探索TARDBP反复出现的变体的潜在创始人效应.
主要方法:
- 在650名与此无关的台湾ALS患者中,TARDBP编码区域的桑格测序.
- 分析患者的人口统计数据,包括发病年龄和疾病呈现 (气柱-发病).
- 使用侧边遗传标记的哈普洛型分析来评估共同祖先.
主要成果:
- 在17名试验者和11名亲属中发现了致病性TARDBP变异.
- 患有致病变异的患者的平均发病年龄较早 (49.1岁),乳球发病比例较高 (32%).
- 复发变种 (p.M337V,p.S375G) 和单种类型分析表明创始人效应,无症状携带者表明穿透不完全.
结论:
- 致病性TARDBP变体是台湾ALS患者的重要遗传因素.
- 这些变异与早期的疾病发作和不完全的透有关.
- M337V和S375G变种可能源于台湾人口中共同的创始人效应.
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